Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2022; 14(2): 511-524
Published online Feb 15, 2022. doi: 10.4251/wjgo.v14.i2.511
Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer
Lauren Midthun, Sungjin Kim, Andrew Hendifar, Arsen Osipov, Samuel J Klempner, Joseph Chao, May Cho, Michelle Guan, Veronica R Placencio-Hickok, Alexandra Gangi, Miguel Burch, De-Chen Lin, Kevin Waters, Katelyn Atkins, Mitchell Kamrava, Jun Gong
Lauren Midthun, Arsen Osipov, Michelle Guan, De-Chen Lin, Jun Gong, Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Sungjin Kim, Biostatistics and Bioinformatics Research Center, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Andrew Hendifar, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Samuel J Klempner, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02114, United States
Joseph Chao, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States
May Cho, Division of Hematology and Oncology, Department of Medicine, University of California, Irvine, CA 92697, United States
Veronica R Placencio-Hickok, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Alexandra Gangi, Miguel Burch, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Kevin Waters, Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Katelyn Atkins, Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Mitchell Kamrava, Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Author contributions: Kim S and Gong J designed the research; Kim S, Guan M, Placencio-Hickok VR and Gong J collected and analyzed the data; Midthun L, Kim S and Gong J wrote the paper; all authors edited and approved the final paper.
Institutional review board statement: The data used in the study are derived from a de-identified National Cancer Database file. As all patient identification variables have been removed, no institutional review board review was needed.
Informed consent statement: The data used in the study are derived from a de-identified National Cancer Database file. As all subject identification variables have been removed, no informed consent was needed.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Gong, MD, Assistant Professor, Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, United States. jun.gong@cshs.org
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 7, 2021
Revised: July 1, 2021
Accepted: December 25, 2022
Article in press: December 25, 2021
Published online: February 15, 2022
Processing time: 331 Days and 13.1 Hours
ARTICLE HIGHLIGHTS
Research background

Palliative chemotherapy has long been known to improve overall survival (OS) in metastatic esophageal cancer, but not all patients with advanced disease receive chemotherapy.

Research motivation

As not all patients with metastatic esophageal cancer are able to receive the benefits of chemotherapy, we evaluated a large cancer database of metastatic esophageal cancer cases to better understand predictors of chemotherapy and survival.

Research objectives

The objectives of this study were to investigate the patient and disease characteristics associated with receipt of palliative chemotherapy in metastatic esophageal cancer. We evaluated the impact of chemotherapy on OS compared to no chemotherapy in our cohort. We also investigated independent predictors of OS on multivariable analyses. Lastly, we investigated whether the effect of chemotherapy on OS in metastatic esophageal cancer patients was time dependent.

Research methods

We identified cases of M1 esophageal cancer in the National Cancer Database (NCDB) between 2004-2015 who had received or did not receive chemotherapy. A logistic regression model was used to examine the associations between chemotherapy and patient factors, and a Cox proportional hazards model was employed to examine the effect of chemotherapy on OS.

Research results

We included 21911 (75%) metastatic esophageal cancer cases receiving chemotherapy and 7271 (25%) not receiving chemotherapy with a median follow-up of 69.45 mo. Several factors were independent predictors of chemotherapy including year of diagnosis 2010-2014, median income > $46000, and node-positivity, while female gender, black race, uninsured status, and high Charlson Comorbidity Index predicted for lower odds of receiving chemotherapy. Although the median OS for patients receiving chemotherapy was 9.53 mo (9.33-9.72) vs 2.43 mo (2.27-2.60) with no chemotherapy, modeling the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo, after which there is no significant effect on OS.

Research conclusions

Palliative chemotherapy confers a significant OS benefit in those with metastatic esophageal cancer. However, the benefit of chemotherapy in this setting is time-dependent and emphasizes the importance of early initiation of chemotherapy.

Research perspectives

Several socioeconomic and clinicopathologic predictors for receiving chemotherapy and OS exist in patients with metastatic esophageal cancer. Future studies should focus on outreach in lower income and underinsured patients to improve receipt of chemotherapy, which is associated with improved OS when initiated in a timely fashion.